Arterial endoglin does not protect against arteriovenous malformations

Area of Science:

• Vascular Biology
• Genetics
• Cell Biology

Background:

• Endoglin (ENG) and ALK1 form a receptor complex crucial for BMP9/10 signaling in endothelial cells (ECs).
• Mutations in ENG or ALK1 cause hereditary haemorrhagic telangiectasia (HHT), a disorder characterized by arteriovenous malformations (AVMs).
• The precise vessel-specific function of ENG and ALK1 in preventing AVMs remains unclear, particularly regarding ENG's role in arterioles versus veins.

Purpose of the Study:

• To investigate the vessel-specific role of endoglin (ENG) in preventing arteriovenous malformations (AVMs).
• To determine if ENG expression in arterial endothelial cells is necessary for protection against AVM formation.
• To compare the incidence and location of AVMs following pan-endothelial versus venous/capillary-specific ENG knockout.

Main Methods:

• Utilized a mouse neonatal retinal model of angiogenesis.
• Employed tamoxifen-inducible Cre-lox system (Apj-Cre-ERT2) for cell-specific gene knockout.
• Compared AVM incidence after pan-endothelial ENG knockout versus selective knockout in venous and capillary ECs.

Main Results:

• Selective depletion of ENG in venous and capillary ECs resulted in retinal AVMs with similar frequency to pan-endothelial ENG loss.
• AVMs were observed in both proximal and distal retina, indicating a defect in vascular remodeling.
• Arterial ENG protein expression was preserved in the venous/capillary-specific knockout model.

Conclusions:

• Endoglin (ENG) expression is not required in arterial endothelial cells to prevent AVM formation.
• The protective role of ENG against AVMs is primarily mediated through its expression in venous and capillary endothelium.
• Findings contribute to understanding the pathogenesis of HHT and the specific functions of endoglin in vascular development.